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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MicroRNA-139-5p suppresses non-small cell lung cancer progression by targeting ATAD2
1Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, PR China.
Abstract:
MiR-139-5p is a suppressor in multiple types of cancer. However, whether miR-139-5p affects NSCLC is unknown. In this study, miR-139-5p expression in clinical samples was examined by real-time PCR and in situ hybridization (ISH). MiR-139-5p mimic was transfected to monitor NSCLC cell behaviors. Potential target was predicated using bioinformatics database. Next, whether miR-139-5p impacted cell behaviors via regulation of its predicted target gene were further evaluated. The result revealed that miR-139-5p was lower in NSCLC samples/cells. MiR-139-5p restrained A549 cell proliferation, accelerated apoptosis, and inhibited the β-catenin signaling. ATAD2 was a predicted target of miR-139-5p, and it was highly expressed in NSCLC tissues. ATAD2 overexpression abolished the miR-139-5p's anti-tumor effect on cell proliferation and apoptosis. TWS119 (a β-catenin signaling activator) partially reversed miR-139-5p overexpression-induced suppression of cell proliferation and promotion of cell apoptosis. In tumor xenografts, miR-139-5p restrained tumor growth. MiR-139-5p was a tumor suppressor in NSCLC by regulating the oncogene ATAD2 and β-catenin signaling. Our study provides a promising target for cancer treatment.
Insights
MicroRNA-139-5p acts as a tumor suppressor in non-small cell lung cancer (NSCLC). It inhibits cancer cell growth by targeting ATAD2 and the β-catenin pathway, offering a potential new treatment strategy.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNA-139-5p (miR-139-5p) is recognized as a tumor suppressor in various cancers.
- Its role in non-small cell lung cancer (NSCLC) remains largely uncharacterized.
Purpose of the Study:
- To investigate the expression and function of miR-139-5p in NSCLC.
- To elucidate the underlying molecular mechanisms, including target genes and signaling pathways involved.
Main Methods:
- Real-time PCR and in situ hybridization (ISH) for miR-139-5p expression analysis.
- In vitro cell culture experiments with miR-139-5p mimic transfection to assess effects on NSCLC cell behavior (proliferation, apoptosis).
- Bioinformatic analysis to predict miR-139-5p targets, followed by experimental validation of ATAD2 and the β-catenin signaling pathway.
Main Results:
- Downregulation of miR-139-5p was observed in NSCLC tissues and cell lines.
- Overexpression of miR-139-5p suppressed NSCLC cell proliferation, induced apoptosis, and inhibited the β-catenin signaling pathway.
- ATAD2 was identified as a direct target of miR-139-5p, and its overexpression counteracted the anti-tumor effects of miR-139-5p.
- Activation of the β-catenin signaling pathway partially reversed the anti-proliferative and pro-apoptotic effects of miR-139-5p.
- In vivo studies demonstrated that miR-139-5p inhibited tumor growth in xenograft models.
Conclusions:
- MiR-139-5p functions as a tumor suppressor in NSCLC.
- Its anti-tumor activity is mediated through the regulation of the oncogene ATAD2 and the β-catenin signaling pathway.
- MiR-139-5p represents a potential therapeutic target for NSCLC treatment.
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